1. Field of the Invention
The present invention relates to a novel process for producing cinnamaldehyde derivatives, which are useful as various intermediates for production of foods, medicaments and the like, in particular, as an intermediate for production of aspartyl dipeptide ester derivatives, which are superior as a sweetener (sweetening agent) having a high sweetening potency (degree of sweetness), and a use thereof as the intermediates and the like.
2. Discussion of the Background
In recent years, as eating habits have been improved to a high level, weight gain caused by excessive sugar intake and diseases accompanied by weight gain have been at issue. Accordingly, the development of a low-calorie sweetener (sweetening agent), which replaces sugar, has been in strong demand. An example of a sweetener that is widely used at present is Aspartame, which is excellent in terms of safety and quality of sweetness. However, Aspartame is somewhat problematic in terms of stability.
An aspartyl dipeptide ester derivative represented by the following general formula (IV) has been found to be a sweetener, and has excellent stability and is better by far in terms of sweetening potency, i.e., has an advantage in cost per sweet taste (see the Description in the International Patent Publication WO99/52937).

In the above formula (IV), R denotes any one of a hydrogen atom, a lower alkyl group having 1 to 4 carbon atoms and a lower alkoxy group having 1 to 4 carbon atoms.
Accordingly, it is an important goal to develop an industrially efficient process for producing such an aspartyl dipeptide ester derivative.
A process for producing the aspartyl dipeptide ester derivative described above efficiently, in particular a production route therefor, and a process for production of the intermediate therefore, have been studied. As a result, it has been found that by reducing a carbon-carbon double bond in a cinnamaldehyde derivative represented by the following general formula (II) selectively, the derivative can be converted into a novel propionaldehyde derivative represented by the following general formula (III) (see the Description in the Japanese Patent Application 11-371284; PCT/JP00/06626), and, on the other hand, that by reacting this aldehyde derivative (III) and an aspartame with hydrogen in the presence of a reduction catalyst for a reductive alkylation reaction, the aspartyl dipeptide ester derivative (IV) which is useful as a sweetener, described above can be industrially and conventionally produced (see the Description in the Japanese Patent Application 11-287398; PCT/JP00/06626).

In the above formulae (II) and (III), R denotes any one of a hydrogen atom, a lower alkyl group having 1 to 4 carbon atoms and a lower alkoxy group having 1 to 4 carbon atoms.
Therefore, it is a purpose of the present invention to produce the cinnamaldehyde derivative represented by the general formula (II) described above industrially and efficiently, and further, by using the compound thus produced, to produce the aspartyl dipeptide ester derivative described above as an objective and an important intermediate thereof (propionaldehyde derivative).
The present inventors have researched and studied on an industrial process for producing the cinnamaldehyde derivative described above. As a result, during the production of such cinnamaldehyde derivative, as shown in the following Reaction Process 1 (see Holzforschung Vol. 46, No. 1, p. 21–24 1992), it has become clear that a process of synthesizing the derivative through 3 steps of reactions starting from cinnamic acid is known. However, it is necessary to use phosgene as a raw material in this process, and thereby this process becomes troublesome, and an yield thereof is also extremely low. Therefore, it is difficult to say that this process is an industrially profitable process to produce the synthetic intermediate described above.
Further, the following Reaction Process 2 (see Cellulose Chem. Technol., 9, 51–59 1975) is also known. In this process, benzaldehydes are used as a starting material, similar to the present invention, but because many reactions are necessary, this process is troublesome, and therefore it is difficult to say that this process is an industrially profitable process.
On the other hand, an aldol reaction is known as a reaction which can be used for a general process of production thereof. For example, in the condition for the aldol reaction described in Organic Reaction, Volume 16 (John Wiley & Sons, Inc. 1968), it is explained that the best result is obtained in the reaction at a temperature of 5 to 25° C. and for a time of 12 to 24 hours. Further, it is thought that the reactivity thereof is affected by a variety of substituent group(s), a position of substitution thereof on a benzene ring and the like, and a prior knowledge showing a fact that an aldol reaction of benzaldehyde derivative having an electron-donating group, such as a hydroxyl group, a methoxy group or the like, with acetaldehyde has been conducted at a high yield, is not found.

In view of the above, the problem to be solved by the present invention is to provide a process for producing the cinnamaldehyde derivative described above industrially and conventionally, and further in a high purity and at a high yield.